Our studies are aimed toward improvement of transplantation therapy for leukemia, utilizing a murine model and induction of leukemia by Rauscher virus. Efforts are directed to three aspects of transplantation therapy. The first aspect deals with determination of the optimal marrow ablative preparatory treatment. This includes the use of chemotherapeutics, irradiation and these two modes in combination. In addition to attempting to find the best dosages and scheduling of these modes, standardly used drugs such as cyclophosphamide and busulphan are being compared with new drugs felt to be promising as pretransplantation chemotherapeutics. The second aspect of these studies involve the testing of various donor strains in order to increase our understanding of the influences of histocompatibility as well as other inherited differences between the donor type and leukemic recipient. In the selection of donors for these studies, we have considered both the resistance of the donor to the leukemia virus and their histocompatibility with the recipients. Since differing patterns of survival and the incidence of leukemic relapse are dependent on both factors, donors have been selected to provide both a range of histoincompatibility with the host as well as a range of sensitivity to the leukemia-inducing virus. Thirdly, we are performing immunobiological tests to advance our knowledge of events involved in the occurrence or non-occurrence of Graft- vs host-response and the development of allogeneic tolerance.